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Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.

Saja MF, Baudino L, Jackson WD, Cook HT, Malik TH, Fossati-Jimack L, Ruseva M, Pickering MC, Woollard KJ, Botto M - Cell Rep (2015)

Bottom Line: Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar.We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs.The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.

View Article: PubMed Central - PubMed

Affiliation: Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.

No MeSH data available.


Related in: MedlinePlus

Modulation of BM and Blood Monocyte Dynamics in P-407-Treated Mice(A–D) Quantitative analysis of cMoPs (A), monocytes (B), and Gr1high (C) and Gr1low monocytes (D) in the BM after 14 and 28 days of P-407 or PBS treatment. Results are expressed as mean ± SE, n = 4 per time point. p values are indicated (unpaired t test); ns, nonsignificant.(E) Frequencies of Gr1high and Gr1low monocyte subsets after splenectomy in mice treated with PBS or P-407 for 14 days. Results are expressed as mean ± SE, n = 4. ∗p < 0.05 and ∗∗∗p < 0.001 (unpaired t test).(F) Percentage of BrdU incorporation into Gr1high (left panel) and Gr1low (right panel) monocytes over a period of 5 days following a single pulse of BrdU administered i.p. in three doses of 2 mg, 3 hr apart. Data are representative of two independent experiments. Results are expressed as mean ± SE, n = 3 in each group (unpaired t test); ns, nonsignificant.See also Figure S3.
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fig2: Modulation of BM and Blood Monocyte Dynamics in P-407-Treated Mice(A–D) Quantitative analysis of cMoPs (A), monocytes (B), and Gr1high (C) and Gr1low monocytes (D) in the BM after 14 and 28 days of P-407 or PBS treatment. Results are expressed as mean ± SE, n = 4 per time point. p values are indicated (unpaired t test); ns, nonsignificant.(E) Frequencies of Gr1high and Gr1low monocyte subsets after splenectomy in mice treated with PBS or P-407 for 14 days. Results are expressed as mean ± SE, n = 4. ∗p < 0.05 and ∗∗∗p < 0.001 (unpaired t test).(F) Percentage of BrdU incorporation into Gr1high (left panel) and Gr1low (right panel) monocytes over a period of 5 days following a single pulse of BrdU administered i.p. in three doses of 2 mg, 3 hr apart. Data are representative of two independent experiments. Results are expressed as mean ± SE, n = 3 in each group (unpaired t test); ns, nonsignificant.See also Figure S3.

Mentions: We first examined the frequency of the BM-resident founder cells termed common monocyte progenitor (cMoP) (Hettinger et al., 2013). The analysis of the BM at 2 and 4 weeks failed to show any significant difference between the two experimental groups in the numbers of cMoPs, total monocytes, and monocyte subpopulations (Figures 2A–2D), demonstrating that the drop in Gr1low monocytes could not be the result of an impaired production in the BM. As the spleen can contribute to the clearance of apoptotic monocytes (Getts et al., 2014) and at the same time act as a “reservoir” for the Gr1high monocytes (Swirski et al., 2009), we assessed the effect of splenectomy on the monocyte distribution. Splenectomized mice treated with P-407 still had a drop in the percentage and number of Gr1low monocytes when compared to the PBS-treated group (Figures 2E and S3A), confirming that P-407 did not promote the splenic clearance of apoptotic Gr1low monocytes (see also Figure 1E).


Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.

Saja MF, Baudino L, Jackson WD, Cook HT, Malik TH, Fossati-Jimack L, Ruseva M, Pickering MC, Woollard KJ, Botto M - Cell Rep (2015)

Modulation of BM and Blood Monocyte Dynamics in P-407-Treated Mice(A–D) Quantitative analysis of cMoPs (A), monocytes (B), and Gr1high (C) and Gr1low monocytes (D) in the BM after 14 and 28 days of P-407 or PBS treatment. Results are expressed as mean ± SE, n = 4 per time point. p values are indicated (unpaired t test); ns, nonsignificant.(E) Frequencies of Gr1high and Gr1low monocyte subsets after splenectomy in mice treated with PBS or P-407 for 14 days. Results are expressed as mean ± SE, n = 4. ∗p < 0.05 and ∗∗∗p < 0.001 (unpaired t test).(F) Percentage of BrdU incorporation into Gr1high (left panel) and Gr1low (right panel) monocytes over a period of 5 days following a single pulse of BrdU administered i.p. in three doses of 2 mg, 3 hr apart. Data are representative of two independent experiments. Results are expressed as mean ± SE, n = 3 in each group (unpaired t test); ns, nonsignificant.See also Figure S3.
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Related In: Results  -  Collection

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fig2: Modulation of BM and Blood Monocyte Dynamics in P-407-Treated Mice(A–D) Quantitative analysis of cMoPs (A), monocytes (B), and Gr1high (C) and Gr1low monocytes (D) in the BM after 14 and 28 days of P-407 or PBS treatment. Results are expressed as mean ± SE, n = 4 per time point. p values are indicated (unpaired t test); ns, nonsignificant.(E) Frequencies of Gr1high and Gr1low monocyte subsets after splenectomy in mice treated with PBS or P-407 for 14 days. Results are expressed as mean ± SE, n = 4. ∗p < 0.05 and ∗∗∗p < 0.001 (unpaired t test).(F) Percentage of BrdU incorporation into Gr1high (left panel) and Gr1low (right panel) monocytes over a period of 5 days following a single pulse of BrdU administered i.p. in three doses of 2 mg, 3 hr apart. Data are representative of two independent experiments. Results are expressed as mean ± SE, n = 3 in each group (unpaired t test); ns, nonsignificant.See also Figure S3.
Mentions: We first examined the frequency of the BM-resident founder cells termed common monocyte progenitor (cMoP) (Hettinger et al., 2013). The analysis of the BM at 2 and 4 weeks failed to show any significant difference between the two experimental groups in the numbers of cMoPs, total monocytes, and monocyte subpopulations (Figures 2A–2D), demonstrating that the drop in Gr1low monocytes could not be the result of an impaired production in the BM. As the spleen can contribute to the clearance of apoptotic monocytes (Getts et al., 2014) and at the same time act as a “reservoir” for the Gr1high monocytes (Swirski et al., 2009), we assessed the effect of splenectomy on the monocyte distribution. Splenectomized mice treated with P-407 still had a drop in the percentage and number of Gr1low monocytes when compared to the PBS-treated group (Figures 2E and S3A), confirming that P-407 did not promote the splenic clearance of apoptotic Gr1low monocytes (see also Figure 1E).

Bottom Line: Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar.We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs.The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.

View Article: PubMed Central - PubMed

Affiliation: Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.

No MeSH data available.


Related in: MedlinePlus